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Forty-six cases of neonatal necrotizing enterocolitis are reported, with a 46% mortality rate. Unlike most other series, low birth weight children accounted for only half the cases. The recognized initiating factors of hypoxia and hemodynamic changes were not always present. A high index of suspicion in the child with non-specific malaise and earlier positive diagnosis provide the most likely means of improving results.
The signs and symptoms associated with necrotizing enterocolitis (NEC) and the common scenarios in which NEC is observed are described to help physicians appreciate the breadth of this illness and to aid in the identification and diagnosis of those affected. An outline for medical management of infants with NEC is presented, based on the pathophysiology of this disease.
BACKGROUND: Necrotizing enterocolitis (NEC) is the most significant acquired gastrointestinal (GI) emergency in the neonatal intensive care unit. METHODS: We sought to gain a clinical perspective on NEC by reviewing the records of NEC patients over a 9-year period. The case histories of 22 infants with NEC treated from September 1, 1986 to September 1, 1995 were reviewed. RESULTS: Mean gestational age was 32 weeks and mean birth weight was 1774 grams. Eighteen percent were full term babies and 82% were premature. Average age at the onset of NEC was 11 days. The most common clinical manifestations were abdominal distension (100%), gastric retention (64%), unstable vital signs (59%) and Guaiac-positive vomitus or stool (36%). Sixteen cases (73%) were classified as stage III NEC, which has the highest mortality and/or morbidity. CONCLUSION: Early identification and management are critical to improve the outcome of NEC.
Nineteen newborn infants with necrotizing enterocolitis, proved by autopsy or surgical examination, are presented. In this study the absence of blood in the stools and of pneumatosis intestinalis did not exclude the diagnosis of necrotizing enterocolitis. The role of umbilical arterial and venous catheters and of exchange transfusion in the pathogenesis of the disease was less than has been previously reported. There was no evidence for emboli of thrombosis in the mesenteric vessels. On the other hand, the probable importance of nonocclusive mesenteric arterial insufficiency is supported by several observations, including the high incidence of antecedent hypoxaemic episodes, the time of onset of the subsequent gastrointestinal pathology and the localization of the lesions. An infectious component was demonstrated, but our results do not allow to state precisely the time of its occurrence.
One hundred one infants requiring operative treatment for necrotizing enterocolitis were evaluated for prenatal, perinatal, therapeutic, clinical, laboratory, radiographic, and operative factors as they relate to mortality. Infants less than 28 weeks gestation and those with birth weight less than 1500 gm had an increased mortality rate. The use of umbilical arterial catheters, high-density premature formulas, and aminophylline (for apnea) had an adverse effect on survival. Persistent acidosis, oliguria, and abdominal wall erythema resulted in a significantly worse outcome. The presence of portal vein air on abdominal radiograph was associated with a 71% mortality rate. The survival rate in infants with localized involvement was 70%. Thirty-eight percent of patients had extensive bowel involvement and a greater than 95% mortality rate. Avoidance of enteral feedings, cautious use of umbilical artery catheters, and judicious application of pharmacologic agents in infants at risk for necrotizing enterocolitis is of importance with regard to prevention. While medical management is feasible in some cases, persistent acidosis, oliguria, abdominal wall erythema, and portal vein air are associated with advanced disease. Infants with these risk factors should be candidates for prompt operative intervention.
OBJECTIVES: Necrotizing enterocolitis (NEC) has been associated with a wide variety of bacteria and their cytotoxins. The content and the nature of gut bacterial colonization in newborns that require intensive care hospitalization has been demonstrated to be abnormal. In the 25-bed neonatal intensive care unit in Hospital Simon Bolivar, in Bogotá, Colombia, cases of NEC are common causes of morbidity and mortality. This article examines the hypothesis that oral administration of prophylactic Lactobacillus acidophilus and Bifidobacterium infantis to all neonates in an intensive care unit, would decrease the incidence of NEC. METHODS: Daily doses of 250 million live L. acidophilus and 250 million B. infantis were given to all 1237 newborns (both inpatients and transfer patients) admitted to the unit during 1 year, until they were discharged from the hospital. In this study, 1282 patients hospitalized during the previous year were used as controls. RESULTS: There were no complications attributed to the daily administration of L. acidophilus and B. infantis. The study groups were compared for place of origin, clinical, and demographic variables, and there was no statistically significant difference in those variables. In the historic control group, there were 85 NEC cases compared to 34 cases in the group that received probiotic prophylaxis (P < 0.0002). In the historic control group, there were 35 NEC-associated fatalities compared to 14 fatalities in the group that received probiotic prophylaxis (P < 0.005). CONCLUSIONS: The positive results in this study support the need for further investigation of bacterial colonization and its role in NEC.
AIM: To investigate the frequency of and risk factors for necrotizing enterocolitis (NEC) among infants of <33 wk of gestation. METHODS: Prospective follow-up of 140 inpatients. RESULTS: 26 (18.6%) subjects developed NEC stage I-III and 12 (8.6%) severe NEC (stage II-III). Breast milk fortifier and duration of morphine infusion emerged as the statistically significant factors associated with NEC stage I-III, but only the latter had a significant association with severe NEC. CONCLUSION: Future studies are needed to be established whether morphine is a causative factor in NEC.
Perforated necrotizing enterocolitis (NEC) in the low-birth weight infant is now one of the most common surgical problems encountered in contemporary neonatal intensive care units. However, morbidity and mortality from NEC remain high, and the optimal surgical management of these infants remains controversial. Currently few data exist comparing the factors influencing outcome in very low-birth weight infants with perforated NEC treated by either local drainage or exploration. We hypothesize that survival of very low-birth weight neonates with perforated NEC may be more dependent on clinical status than on treatment modality. We present our experience treating a large cohort of infants weighing less than 1000 g with perforated NEC. A retrospective cohort study describes our experience with perforated NEC in very low-birth weight infants in a Level III neonatal intensive care unit. Between January 1991 and May 1998 a total of 70 newbo infants weighing less than 1000 g were evaluated and managed for perforated NEC. Comorbid factors were identified and calculated for each infant. Primary treatment was either local drainage or laparotomy. Statistical analysis was performed by Student's t test and multiple logistic regression. A multiple logistic regression model examined factors (comorbidities, number of comorbidities, and mode intervention) influencing outcome. A Kaplan-Meier survival analysis comparing survival versus number of comorbidities was performed. Twenty-two infants with an average weight of 679 g were treated by local drainage. Forty-eight infants with an average weight of 756 g were treated with exploratory laparotomy. Infants treated by local drainage had a higher cumulative number of comorbid factors (5.2+/-0.50 vs 3.7+/-0.29; P < 0.05) than those managed by operative exploration. Fourteen infants (63%) initially undergoing local drainage for perforated NEC survived. Of the 48 infants 36 operated on survived (75%). No single factor or combination of any comorbid factors was predictive of outcome. The total number of comorbidities for each neonate did reach statistical significance (P < 0.05). A greater likelihood of death was associated with a higher number of comorbidities. Survival with four or fewer comorbidities was 84 per cent, whereas survival with greater than six comorbidities was 30 per cent. The mean number of comorbidities was greater for drainage than for surgery, and for the same number of comorbidities the probability of survival tended to be greater for those treated with drainage than for those undergoing surgery. Multiple logistic regression analysis identified the total number of comorbidities as affecting outcome rather than treatment choice. This suggests therefore that selection of therapeutic options for the patient requires evaluating all factors that may impact survival rather than applying a single treatment strategy for all patients.
We report a 58-year-old woman with pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis. She was receiving treatment for liver cirrhosis and hepatic failure when sudden severe right upper abdominal pain and fever developed. Abdominal radiograph disclosed pneumatosis intestinalis, involving the ascending colon, and small collections of free air along the right hemidiaphragm. The pneumatosis intestinalis appeared in both cystic and linear form. Autopsy revealed necrosis and multiple gas-filled mural cysts in the ascending colon. To our knowledge, this is the first case to be reported of pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis.
The intestinal contents of 17 neonates with necrotizing enterocolitis were analyzed for pH, carbohydrate, protein, and bacteria. The intraluminal pH was less than 5.0 (16/17). Sufficient carbohydrate and bacteria capable of fermenting the carbohydrate to organic acids were found. The intraluminal protein content was greater than 5 g/dl. The variables of acid and protein were then examined in a rabbit intestinal loop model. The hemorrhagic response in individual loops was measured using Cr51 tagged red blood cells such that the microliters of blood per centimeter intestine could be determined. Loops with organic acid and protein had significantly (p less than 0.01) more intramural blood than control loops. Organic acid (possibly generated by bacterial mixed acid fermentation of carbohydrate) in the presence of protein promotes intramural hemorrhage similar to that seen in neonates with necrotizing enterocolitis.
There is controversy about the identity of focal intestinal perforation (FIP) and necrotizing enterocolitis (NEC). To elucidate the difference between them, we reviewed their clinical presentations. Over the last 20 years, 39 very-low-birth-weight (VLBW) neonates, including 21 extremely-low-birth-weight neonates, underwent a laparotomy for intestinal perforation without mechanical causes. Nineteen patients had typical findings of NEC, and 8 had FIP. FIP is defined as isolated intestinal perforation without gross necrosis. In FIP, the gestational age was significantly lower than in NEC (23.8 +/- 1.8 vs 27.0 +/- 2.5 weeks, P < 0.01). The birth weight (BW) of FIP patients was lower than that of NEC infants (635 +/- 134 vs 883 +/- 256 g, P < 0.05). The incidence of coexistent respiratory distress syndrome (RDS) was higher in FIP compared to NEC (88% vs 37%, P < 0.05). The age at onset was younger in FIP than NEC (7.3 +/- 2.7 vs 14.4 +/- 7.9 days, P < 0.05). All patients except 1 had the sites of perforation exteriorized. There was a trend toward higher survival in FIP compared to NEC (88% vs 58%, P = 0.136). Our data clearly show differences in BW, gestational age, and association of RDS between FIP and NEC. Based on our data, prematurity and RDS appear to be the major etiologic factors of FIP. The present series supports the fact that FIP is a definite clinical entity.
A case of spontaneous bile-duct perforation in a 5-month-old boy with a history of necrotizing enterocolitis in his 1st week of life is reported. To our knowledge, this is the second case reported with such an antecedent, supporting a vascular etiology for some cases of spontaneous biliary perforation.
OBJECTIVE: To determine whether the rate of feed advancement affects the incidence of necrotizing enterocolitis (NEC). STUDY DESIGN: Prospective randomized controlled trial involving 185 formula-fed infants with birth weight 501 to 1500 g and gestational age </=34 weeks. Infants were randomized into 2 groups: "slow" (n = 98), who received 15 cc/kg/d increments (a 10-day schedule to full feeds) and "fast" (n = 87), who received 35 cc/kg/d increments (a 5-day schedule to full feeds) of Similac Special Care 20 cal/oz. Feeds were increased only if well tolerated as defined by a protocol. RESULTS: The incidence of NEC (Bell stage >/=II) was similar in both groups (slow 13% and fast 9%, P =.5). The incidence of perforation (Bell stage III) was also similar in both groups (slow 4% and fast 2%, P =.8). Feeds were started at a comparable postnatal age in both groups (median age: slow 5 days and fast 4 days, P =.9). Although the neonates in the fast group attained full enteral intake earlier (median days [25th and 75th percentiles]: slow 15 [12, 21] and fast 11 [8, 15], P <.001) and regained their birth weight earlier (slow 15 [11, 20] and fast 12 [8, 15], P <.05), their ages at discharge were not statistically different (slow 47 [31, 67] and fast 43 [29, 62], P =.3) CONCLUSIONS: A greater than twofold difference in the rate of feed advancement from 15 cc/kg/d to 35 cc/kg/d did not affect the incidence of NEC >/= stage II. Factors other than feed advancement appear to be more important in the pathogenesis or progression of NEC.
OBJECTIVES: To determine whether supplementation with L -arginine reduces the incidence of all stages of necrotizing enterocolitis (NEC) in premature infants with birth weight < or =1250 g and gestational age < or =32 weeks. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, 152 premature infants were prospectively, randomly assigned to receive either supplemental L -arginine (1.5 mmol/kg per day; n =75 [group A]) or placebo (control group; n = 77 [group B]) with oral feeds/parenteral nutrition during the first 28 days of life. Nutrient intake, plasma ammonia, arginine, and amino acid concentrations were measured in all infants at days 3, 14, and 28 and at the time of diagnosis of NEC. RESULTS: NEC developed in 5 infants in group A compared with 21 infants in group B (P <.001). Arginine intake and plasma arginine concentrations were similar in both groups at study entry and (as expected) increased in group A at days 14 and 28. Plasma arginine concentrations were lower in both groups at time of diagnosis of NEC. No significant differences in maternal and neonatal demographics, nutrient intake, plasma ammonia and total and essential amino acid concentrations were present between the two groups. CONCLUSIONS: Arginine supplementation (1.5 mmol/kg per day) in premature infants reduces the incidence of all stages of NEC.
Our aim was to investigate the effect of C1-inhibitor (C1-INH) in a rat model of necrotizing enterocolitis (NEC). Twenty-four anesthetized and artificially ventilated rats received 0.1 mg/kg endotoxin. Fifteen minutes later, the animals in the study group (n = 12) were treated with 200 IU/kg C1-INH whereas the control animals (n = 12) received normal saline. In all animals, FiO(2) was reduced after 90 min from 0.21 to 0.05 and ventilation continued until 180 min or death. All animals developed shock symptoms. Drop in mean arterial blood pressure was more pronounced and survival time was shorter in the control group. Whereas the C1-INH activity increased in the study group, it decreased in the control group. The extent of macroscopic intestinal lesions did not differ between the groups. In conclusion, C1-INH did not prevent shock, but mitigated and delayed its course.
We examined (1) the observer variability (both interobserver and intraobserver) in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis (NEC), (2) the interobserver variability for individual radiologic signs used to diagnose NEC, and (3) the influence of experience in determining the extent of observer variability. Our hypotheses were (1) there would be considerable observer variability in interpretation of abdominal radiographs of infants with suspected NEC; (2) the extent of observer variability would differ for individual radiologic signs of NEC; and (3) the extent of observer variability would be determined by the observer's experience. The participants included 12 observers: two pediatric radiologists, four attending neonatologists, three neonatal fellows, and three pediatric residents. The participating observers under similar interpretation conditions, twice independently, interpreted the same 40 pairs of abdominal radiographs from infants with suspected NEC. The interval between the two interpretations was 3 to 6 months. Intraobserver and interobserver variability was assessed by applying the Kappa statistic to the radiologic signs of NEC for the two separate interpretations. The observers were blinded to patient's identity and the clinical course. Each observer recorded the absence, suspicion, or presence of (1) intestinal distention, (2) air fluid levels, (3) bowel wall thickening, (4) pneumatosis intestinalis, (5) portal venous gas, (6) pneumoperitoneum, and (7) NEC. We found low intraobserver and interobserver agreements. There was considerable variation in observer variability for individual radiologic signs. Trained observers performed better than intraining observers. We conclude that the radiologic signs in isolation should not be considered reliable. We recommend studies to formulate more objective criteria for many of the radiographic features of NEC. Standardization and periodic enforcement of these criteria among observers could reduce observer variability. We suggest that, to decrease both false-negative and false-positive interpretation, an experienced observer should always review the radiographs of infants with suspected NEC.
OBJECTIVE: To determine the impact of necrotizing enterocolitis (NEC) on length of stay and hospital charges. DESIGN: Case-control study. SETTING: Two neonatal intensive care units in an academic medical center. PATIENTS: Infants born in 1992--1994 with birth weight <1500 g, matched by gestational age, hospital, and month of birth. MEASUREMENTS AND MAIN RESULTS. We performed odds ratio and t testing. As with previous studies, there was no single factor that increased the risk for developing NEC. However, the diagnosis of NEC increased the risk for death, infection, and the need for central line placement. Infants with surgical NEC had lengths of stay that exceeded those of controls by 60 days, whereas lengths of stay among infants with medical NEC exceeded those of controls by 22 days. Based on length of stay, the estimated total hospital charges for infants with surgical NEC averaged $186 200 in excess of those for controls and $73 700 more for infants with medical NEC. The yearly additional hospital charges for NEC were $6.5 million or $216 666 per survivor. CONCLUSIONS: A diagnosis of NEC in the very low birth weight infant imposes a significant additional financial burden to the individual patient as well as the neonatal community as a whole. This expense justifies additional research into preventive measures and potentially costly therapies aimed at reducing the incidence of NEC. These data also provide an estimated cost to compare the cost effectiveness of new preventive measures for NEC.
OBJECTIVE: To evaluate and compare the outcome of newborns with definite (Bells stage II) and advanced (Bells stage III) necrotizing enterocolitis (NEC) and to assess the role of primary peritoneal drainage. METHODS: This study was conducted in the Department of Pediatric Surgery, Maternity and Children's Hospital, Dammam, Kingdom of Saudi Arabia. Medical records of all cases diagnosed with NEC or suspected NEC between May 1993 and June 2003 were reviewed retrospectively. A total of 67 cases meeting the criteria for Modified Bells stage II and III disease were selected for the study. Twenty-five (37%) cases were treated medically and 42 (63%) needed surgical intervention, namely primary peritoneal drainage (PPD) with or without salvage laparotomy (SL) (n=25), or primary laparotomy (PL) (n=17). Data regarding patient demographics, neonatal history, clinical presentation, laboratory and radiological features, operative findings, complications and mortality were collected and compared between the medical and surgical group and between the 2 surgical groups. RESULTS: The overall mortality was 37%, 8% in the medical group versus 55% in the surgically treated group. The PPD group had the highest mortality (72%) versus 29% in the PL group. In the PPD group, 14 (56%) needed SL and only 3 (12%) survived without laparotomy. The mean gestational age and birthweight were 32.1 weeks and 1713 gms in the PPD group as compared to 35.7 weeks and 2484 gms in the PL group. The PPD group were more critically sick than the PL group. The average length of time from onset to laparotomy was longer, 6.6 days in the PPD group versus 2.2 days in the PL group. In the 31 cases undergoing laparotomy, the terminal ileum was involved most frequently followed by the cecum and right colon. The PPD + SL group had a higher mortality in isolated, multifocal, and pan involvement of bowel when compared to the PL group. All babies with only isolated involvement in the PL group survived. CONCLUSION: The surgical mortality of NEC in our hospital is very high due to advanced disease. The PPD group in our study fared badly, as it comprised a poor risk group with ongoing sepsis, with the bias being in favor of PPD as these babies were unfit to undergo major surgery. Early SL after PPD in those showing signs of persistent disease may improve the outcome in this group.